Volatile Anesthetics Research Articles

Sevoflurane exposure may cause dysplasia of dendritic spines and result in fine motor dysfunction in developing mouse through the PI3K/AKT/mTOR pathway.

Sevoflurane has become one of the most widely used volatile anesthetics in pediatric surgery. However, sevoflurane exposure may interfere with dendritic development and synaptogenesis, resulting in brain function impairment. The PI3K/AKT/mTOR pathway plays an important role in dendritic development and synaptic plasticity. Here we investigated whether sevoflurane exposure would affect the morphological proportions of dendritic spines in developing mouse and explored the role of the change of plasticity of dendritic spines in sevoflurane-induced neurodevelopmental toxicity. The related signaling pathway was also examined. C57BL/6 mice at postnatal day (PND) 7 were exposed to 2% sevoflurane for 3 h. The PI3k/AKT/mTOR agonist IGF-1 or the mTOR phosphorylation inhibitor KU0063794 was intraperitoneally injected 30 min before sevoflurane or O2 exposure at PND7. Hippocampi were harvested 6 h after sevoflurane exposure. Western blotting was applied to measure the protein expression of PI3K/AKT/mTOR pathway phosphorylation. At PND14, brains from all groups were harvested for Golgi staining, and the morphology of dendritic spines of hippocampal neurons was observed by an oil immersion lens. When the mice grew to adolescence (PND48), fine motor function was measured by the Beam walking test. Here we showed that exposure to 2% sevoflurane for 3 h decreased the proportion of thin dendritic spines and increased the proportion of mushroom dendritic spines, but not changed the density of the dendritic spines. Sevoflurane exposure also suppressed the phosphorylation of the PI3K/AKT/mTOR pathway in immature mice hippocampi, and eventually led to long-term fine motor dysfunction. Meanwhile, IGF-1 pretreatment could rescue and KU0063794 pretreatment could aggravate the impairment induced by sevoflurane. In conclusion, sevoflurane exposure may cause a change of proportions of the types of dendritic spines through impacting the phosphorylation expression of the PI3K/AKT/mTOR pathway, and eventually led to long-term fine motor dysfunction in developing mouse.

David O. Warner, M.D., Recipient of the 2022 Excellence in Research Award

David O. Warner, M.D., Recipient of the 2022 Excellence in Research Award

Journal-related Activities and Other Special Activities at the 2022 American Society of Anesthesiologists Meeting

Journal-related Activities and Other Special Activities at the 2022 American Society of Anesthesiologists Meeting

Malignant hyperthermia – state of knowledge

Malignant hyperthermia (MH) is a relatively rare, but potentially lethal genetic disorder. That disease is characterized by hypermetabolic response of the skeletal muscles caused by exposure to triggering agents e.g. volatile anesthetics or depolarizing neuromuscular blockers.
 The object of this article was to review and assess the most recent published works about the epidemiology, etiology, pathomechanism, therapy of the MH and the new advances in all these fields.
 Authors scrutinized PubMed and Google Scholar using keywords: malignant hyperthermia, volatile anesthetics, ryanodine receptor mutation. In addition to this, the references of chosen articles were manually scoured for supplementary applicable articles. The literature was selected on the basis of a general medicine readership and prioritized clinical practice guidelines, systematic reviews and case reports.
 The references include the latest reports on malignant hyperthermia, apart from works of historical importance.
 Available treatment methods consist mainly of pharmacotherapy, symptomatic treatment and monitoring of vital parameters. Dantrolene is a first-choice drug in initial treatment of MH and is considered the only specific antidote.
 In spite of the constant advances in the areas of medicine there is still much to be discovered about MH. Further studies are necessary, as the amount of credible evidence is not adequate.

Association between post-operative delirium and use of volatile anesthetics in the elderly: A real-world big data approach

Study objectiveEarly post-operative delirium is a common perioperative complication in the post anesthesia care unit. To date it is unknown if a specific anesthetic regime can affect the incidence of delirium after surgery. Our objective was to examine the effect of volatile anesthetics on post-operative delirium. DesignSingle Center Observational Study. SettingPost Anesthesia Care Units at a German tertiary medical center. Patients30,075 patients receiving general anesthesia for surgery. MeasurementsDelirium was assessed with the Nursing Delirium Screening Scale at the end of the recovery period. Subgroup-specific effects of volatile anesthetics on post-operative delirium were estimated using generalized-linear-model trees with inverse probability of treatment weighting. We further assessed the age-specific effect of volatiles using logistic regression models. Main resultsOut of 30,075 records, 956 patients (3.2%) developed delirium in the post anesthesia care unit. On average, patients who developed delirium were older than patients without delirium. We found volatile anesthetics to increase the risk (Odds exp. (B) for delirium in the elderly 1.8-fold compared to total intravenous anesthesia. Odds increases with unplanned surgery 3.0-fold. In the very old (87 years or older), the increase in delirium is 6.2-fold. This result was confirmed with internal validation and in a logistic regression model. ConclusionsOur exploratory study indicates that early postoperative delirium is associated with the use of volatile anesthetics especially in the sub-cohort of patients aged 75 years and above. Further studies should include both volatile and intravenous anesthetics to find the ideal anesthetic in elderly patients.

Volatile anesthetics for ICU sedation: the future of critical care or niche therapy?

Volatile anesthetics for ICU sedation: the future of critical care or niche therapy?

The science behind banning desflurane: A narrative review.

Potent inhaled anaesthetics are halogenated hydrocarbons with a large global warming effect. The use of fluorinated hydrocarbons (most are not anaesthetics) are being restricted but volatile anaesthetics have been exempted from legislation, until now: the EU has formulated a proposal to ban or at least severely restrict the use of desflurane starting January 2026. This narrative review addresses the implications of a politics-driven decision - without prior consultation with major stakeholders, such as the European Society of Anaesthesiology and Intensive Care (ESAIC) - on daily anaesthesia practice and reviews the potential scientific arguments that would support stopping the routine use of desflurane in anaesthetic practice. Of note, banning or severely restricting the use of one anaesthetic agent should not distract the user from sensible interventions like reducing fresh gas flows and developing technology to capture and recycle or destroy the wasted potent inhaled anaesthetics that we will continue to use. We call to join efforts to minimise our professional environmental footprint.

This Month in Anesthesiology

This Month in Anesthesiology

COMPARISON OF 6% AND 8% SEVOFLURANE FOR INHALATIONAL INDUCTION IN ADULTS

Inhaled anaesthetics are the widely used drugs for the induction and maintenance of general anaesthesia. The evolution of volatile anaesthetics began with the introduction of Diethyl ether46, Nitrous oxide to the modern inhaled anaesthetics like Desurane and Sevourane(1). These modern inhaled anaesthetics form the important tool for altering the central nervous system functions in patient undergoing general anaesthesia. In 1950, all halogenated anaesthetics with an exception of Nitrous oxide were ammable and potentially toxic to the liver. Replacing the hydrogen atom with a uorine atom led to introduction of newer anaesthetics which are non-inammable and are resistant to metabolism(2).

Routine use of depth of anaesthesia monitoring in patients receiving volatile anaesthesia: is it worth it?

This article discusses the place of routine use of depth of anaesthesia monitoring in patients receiving volatile anaesthesia. Benefits include reducing the probability of accidental awareness or excessive depth of anaesthesia, and creating training opportunities to improve familiarity with its use, but these must be weighed against the costs, as it may not be advantageous from a cost–benefit perspective.

Greenhouse gas reduction in anaesthesia practice: a departmental environmental strategy

Sustainability interventions were implemented at the Royal Brisbane and Women’s Hospital (RBWH) following identification of inhaled anaesthetic gases as a target for reducing medical carbon emissions. This quality improvement study...

Propofol directly binds to and inhibits TLR7.

Sedatives/anesthetics are important medical tools to facilitate medical care and increase patients' comfort. Increasingly, there is recognition that sedatives/anesthetics can modulate immune functions. Toll-like receptors (TLRs) are major pattern recognition receptors involved in the recognition of microbial components. TLR7 recognizes single-strand RNA virus such as influenza and SARS-CoV2 viruses and initiates interferon (IFN) responses. IFN production triggered by TLR7 stimulation is a critical anti-viral response. For example, patients with TLR7 variants including loss-of- function variants were associated with severe COVID-19. Taken together, it is important to determine if sedatives/anesthetics mitigate TLR7 function. We have previously showed that TLR7-mediated activation was not affected by volatile anesthetics. However, we found that propofol attenuated TLR7 activation among intravenous sedatives in the reporter assay. TLR7 agonist R837 stimulation increased TNF-α, IL-1β, IL-6, IL-10, and IFN-β mRNA levels in bone marrow-derived dendritic cells, while these levels were attenuated by propofol. Our murine lung slice experiments showed that propofol attenuated IFN production. R837 increased IFN-β expression in the lungs, and propofol attenuated IFN-β expression in an in vivo model of R837 intranasal instillation. We also found that propofol directly bound to and hindered its association of TLR7 with MyD88. Our analysis using fropofol, propofol derivative showed that the hydroxyl group in propofol was important for propofol-TLR7 interaction.

Anesthetic and analgesic techniques and perioperative inflammation may affect the timing of recurrence after complete resection for non-small-cell lung cancer.

IntroductionIt has been widely recognized that both surgery and anesthesia may increase the risk of cancer recurrence by inducing an inflammatory response and immunosuppression in various cancer operations. The present study explored using hazard curves how anesthetic and analgesic techniques regarding the host inflammation status affect the risk of recurrence over time in patients with non-small-cell lung cancer (NSCLC).Material and MethodsClinicopathological data from patients who underwent complete pulmonary resection with pathological I–IIIB stage NSCLC from 2010 to 2020 were collected. The inflammation-based scores, including the C-reactive protein-to-albumin ratio (CAR), systemic immune-inflammation index (SII), Glasgow prognostic score (GPS), and modified GPS (mGPS), were calculated before surgery, and hazard curves indicating the changes in hazards over time were evaluated.ResultsA total of 396 patients were eligible for the analysis. The median follow-up was 42.3 months. In total, 118 patients (29.8%) experienced recurrence, and 66.9% of those occurred within 24 months after surgery. According to the multivariate Cox regression analysis, volatile anesthesia (VA) (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.05–2.71), and elevated CAR (HR, 1.88; 95% CI, 1.18–2.99) were associated with a worse recurrence-free survival. The resulting hazard curve revealed that a delayed peak of recurrence was present in patients with a low CAR in the VA group and in those with intravenous flurbiprofen axetil administration in the propofol-based total intravenous anesthesia group (30 and 24 months after surgery, respectively).DiscussionChoosing anesthetic and analgesic techniques while taking inflammation-based scores into account may be useful for reducing the risk of and/or delaying recurrence in patients undergoing resection for NSCLC.

Volatile anesthesia versus propofol-based total intravenous anesthesia: A retrospective analysis of charts of patients who underwent elective digestive tract cancer curative surgeries.

The surgical stress responses, surgeries, and anesthetics used during surgeries have effects on post-surgery complications and metastasis. Volatile and/or intravenous anesthetics are generally used for cancer curative surgeries. Therefore, appropriate selection of anesthetics should be considered for better clinical outcomes. The objectives of the study were to compare postoperative complications, the overall survival, and recurrence-free survival of patients who had received volatile anesthesia against those of patients who had received propofol-based total intravenous anesthesia for digestive tract cancer curative surgeries. Patients had received propofol-based total intravenous anesthesia (PA cohort, n = 120) or volatile anesthesia (VA cohort, n = 185) for elective digestive tract cancer curative surgeries. Patients with age > 50 years (P = .0399), body mass index ≥ 25 kg/m2 (P = .0423), cancer stage III (P = .0041), and cancer stage IV (P = .0189) were operated through volatile anesthesia. Females (P = .0346), disable patients (P = .0479), patients with Charlson Comorbidity Index 2 (P = .0449), patients with cancer stage 0 or I (P = .0141), and patients with cancer stage II (P = .0289) were operated through propofol-based total intravenous anesthesia. Postoperative complication(s) between patients of both cohorts were statistically same (P = .9217). After 3-years of the follow-up period, a total of 81 (44%) patients from the VA cohort and 63 (52%) patients from the PA cohort survived irrespective of any kind of disease(s) (P = .9918). Also, a total of 53 (29%) patients from the VA cohort and 42 (35%) patients from the PA cohort survived without progression of cancer (P = .9981) after 3-years. Age > 50 years (P = 0.0491), Charlson Comorbidity Index ≥ 3 (P = 0.0481), and cancer stage > II (P = .0412) were independent parameters for death of patients suffering from digestive tract cancer due to any reason(s) during 3-years of the follow-up period after surgeries. The selection of anesthetic agents for cancer curative surgeries does not affect survival during 3-years of follow-up and postoperative complication(s) of patients suffering from digestive tract cancer (Level of Evidence: III; Technical Efficacy Stage: 4).

Volatile versus Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery: Analysis of 1586 MYRIAD Trial Patients Managed with the Same Perioperative Protocol.

This study investigated the influence of volatile anesthesia (VA) on major complications and mortality in patients undergoing coronary artery bypass graft surgery (CABG). This post-hoc analysis included 1586 patients from the MYRIAD trial managed using the same perioperative protocol at a single institution. Patients were randomized to receive either volatile anesthesia (sevoflurane, isoflurane, or desflurane) or total intravenous anesthesia (TIVA). The assessed study outcomes were the rate of complications, including: myocardial infarction, stroke, acute kidney injury, prolonged ventilation ( 24 h), receipt of high-dose inotropic support (inotropic score 10), and need for mechanical circulatory support. The duration of intensive care unit (ICU) stay, length of hospitalization, hospital readmission during follow-up, 30-days and 1-year mortality were also analyzed. 1586 patients were enrolled between September 2014-September 2017 and randomly assigned to the volatile anesthesia group (n = 794) and the TIVA group (n = 792). The median patient age was 63 years, with a median ejection fraction of 60%. There were no significant differences in the rates of major complications, duration of ICU stay, and hospitalization between the groups. The median total dose of fentanyl was 12.0 mcg/kg in volatile group and 14.4 mcg/kg in TIVA group (p 0.001). One-year mortality rates were 2.5% (n = 20) and 3.2% (n = 25) in the volatile and TIVA groups, respectively. Two patients were lost at the 30-day and 1-year follow-ups in the volatile group compared to four patients in TIVA group. Regression analysis showed that cardiopulmonary bypass (CPB) duration, fentanyl dose, and baseline serum creatinine level were associated with 30-days mortality, while ejection fraction was associated with 1-year mortality. The use of VA in patients undergoing CABG did not result in a reduction in major complications or mortality compared with TIVA. A higher dose of fentanyl was used in the TIVA group and was associated with an increase in the 30-days mortality. These findings warrant further investigation. ClinicalTrials.gov (NCT02105610).

Comparison of Emergence Agitation Scale Scores and Creatine Kinase Levels After General Anesthesia in Children: A Prospective Cohort Study.

IntroductionA simple indicator of muscle damage is creatine kinase (CK). Although CK elevation is informative for malignant hyperthermia, no study has examined the relationship between the anesthetically awake state and CK in children. We aimed to prospectively examine the relationship between the awakening state and CK on the day after surgery in children who have undergone anesthesia with volatile inhalation anesthetics.MethodsThe study included 119 patients aged 0-15 years and scheduled to undergo general anesthesia for cleft lip and palate-related surgery. Emergence agitation (EA) was assessed after completion of general anesthesia using the five-point EA scale, and patients were divided into the following five groups according to the EA score: EA1, EA2, EA3, EA4, and EA5. The primary outcome was ΔCK (comparison of CK values one week prior to surgery to CK values on the day after surgery) in each EA group. The secondary outcome was ΔCK when the EA score was divided into the following two groups: EA ≤2 (EA score of 1 or 2) and EA ≥3 (EA score of 3, 4, or 5).ResultsThe median ΔCK values in the EA1 to EA5 groups were 3 (quartile −19~9), 5 (−32~88), 99.5 (−18~190.5), 121 (29~219.5), and 144 (41~340.5), respectively, indicating a statistically significant difference overall. Statistically significant differences were also observed between the EA1 and EA4 groups and between the EA2 and EA4 groups. The median ΔCK values in the EA ≤2 and EA ≥3 groups were 3 (quartile −27~85) and 108 (23.5~206.7), respectively, indicating a statistically significant difference.ConclusionThe results of this study revealed that a higher EA score at the time of anesthesia awakening is associated with a larger ΔCK, indicating that a high CK level on the day after surgery is highly related to the state of the patient upon awakening.

Assessing Postoperative Recovery With Volatile Gas Versus Total Intravenous Anesthesia in Patients With and Without Obstructive Sleep Apnea.

To determine if there is a recovery time difference between patients with and without obstructive sleep apnea (OSA) when using total intravenous anesthesia (TIVA) compared to volatile gas inhalational anesthesia. OSA and Non-OSA patients were identified at a tertiary institution between January 2019 and November 2020. Non-OSA patients were defined as those who have not been formerly diagnosed with OSA. A modified STOP-BANG score (MSBS) was performed to screen Non-OSA patients for OSA. Recovery was measured by Phase I recovery time, or time it took a patient to reach ≥9/10 on the Aldrete scoring system. A total of 334 patients were included with 142 in the OSA cohort (59 TIVA, 83 inhalational anesthesia) and 192 in the Non-OSA cohort (119 TIVA, 73 inhalational anesthesia). In OSA patients, there was a 41.29-minute recovery time reduction when using TIVA versus sevoflurane (P < .0001). Non-OSA patients recovered faster than OSA patients when undergoing inhalational anesthesia by 46.76 minutes and TIVA by 18.58 minutes (P < .0001 and P = .0907, respectively). Non-OSA patients with a MSBS < 3 and ≥3 had a shorter recovery time compared to OSA patients when both underwent sevoflurane anesthesia (57.27 minutes, P < .0001 and 56.23 minutes, P = .040, respectively). Non-OSA patients with a MSBS of <3 had a decrease in recovery time of 26.68 minutes when compared to OSA patients who underwent TIVA (P = .0004). When utilizing TIVA over inhalational anesthesia, patients with OSA have significantly increased benefit in terms of reduced Phase I recovery times as compared to Non-OSA patients.

Anesthetic Management in Parturients With Fontan Physiology

Anesthetic Management in Parturients With Fontan Physiology

This Month in Anesthesiology

This Month in Anesthesiology

Anesthetic Preferences for Cardiac Anesthesia: A Survey of the Society of Cardiovascular Anesthesiologists.

Volatile anesthetics have been historically preferred for cardiac anesthesia, but the evidence for their superiority to intravenous agents is mixed. We conducted a survey to better understand the current state of practice and the rationale behind provider preferences for anesthesia for cardiac surgery with cardiopulmonary bypass. We hypothesized that anesthetic preference would vary considerably among surveyed providers without a clear majority, as would the rationale behind those preferences. Email invitations were sent to members of the Society of Cardiovascular Anesthesiologists, who were asked to identify the anesthetics or sedatives they typically prefer to administer during induction, prebypass, bypass, postbypass, and postoperative periods and why they prefer those agents. Members' beliefs regarding the importance of anesthetics on postoperative outcomes were also assessed. Invitations were sent on 2 separate dates to 3328 and 3274 members, of whom 689 (21%) responded. The median (interquartile range [IQR]) respondent age was 45 (37-56) years, 79% were men, and 75% were fellowship trained. The most frequently chosen drug for induction was propofol (80%). Isoflurane was the most frequently selected primary agent for the prebypass (57%), bypass (62%), and postbypass periods (50%). Sevoflurane was the second most frequently selected (30%; 17%, and 24%, respectively). Propofol was the third most frequently selected agent for the bypass (14%) and postbypass periods (17%). Ease of use was the most frequently selected reason for administering isoflurane and sevoflurane for each period. During bypass, the second most frequently selected rationale for using isoflurane and sevoflurane was institutional practice. A total of 76% responded that the perfusionist typically delivers the bypass anesthetic. Ischemic preconditioning, organ protection, and postoperative cognitive function were infrequently selected as rationales for preferring the volatile anesthetics. Most respondents (73%) think that anesthetics have organ-protective properties, especially isoflurane (74%) and sevoflurane (59%), and 72% believed that anesthetic choice contributes to patient outcome. The median (IQR) agreement (0 = strongly disagree to 100 = strongly agree) was 72 (63-85) for the statement that "inhaled anesthetics are an optimal maintenance anesthetic for cardiac surgery." In a survey of cardiac anesthesiologists, a majority of respondents indicated that they prefer volatile anesthetics for maintenance of anesthesia, that anesthetic selection impacts patient outcomes, and that volatile anesthetics have organ-protective properties. The members' rationales for preferring these agents possibly reflect that practical considerations, such as ease of use, effectiveness, and institutional practice, also influence anesthetic selection during cardiac surgery in addition to considerations such as organ protection.